JP7072582B2 - Iodine composition - Google Patents

Description

Iodine compositions are useful as topical disinfectants and disinfectants. Iodine tincture is a composition based on a water-alcohol solution of ethanol and elemental iodine in water, iodide salts, which has long been used for such purposes. Such tinctures, however, are highly irritating and toxic and are therefore unsuitable for administration to sensitive tissues such as the eye. Many iodine compositions in the art are alternatives, as PVP-iodine or polyvinylpyrrolidone-iodine, as a source and reservoir of iodine for free molecules and to improve the solubility of iodine in an aqueous environment. Is also based on the known povidone iodine.

Examples of ophthalmic compositions comprising povidone iodine are described, for example, in European Patent Application Publication No. 0526695 and International Publication No. 2010084473 pamphlet. Such compositions rely on a wide range of formulations and require the addition of pH buffers or modifiers, stabilizers, and other excipients to provide stability and sufficient shelf life. ..

Iodine compositions based on non-aqueous media such as organic solvents have also been previously disclosed. For example, US Patent Application Publication No. 2012/0219640 contains iodine compositions for use in the treatment of localized skin conditions such as waterworm infections, including organic solvents such as ethanol, isopropyl alcohol and acetone. The thing is disclosed. Such solvents cannot be widely applied in terms of therapeutic use due to tissue toxicity or poor biocompatibility. WO 2012/007776 proposes the use of siloxane carriers for the preparation of iodine sterilizing and disinfecting solutions. Siloxane, however, can tend to be viscous, feel greasy due to topical application, and may have limited extensibility. They also tend to have a different index of refraction than human tears and may therefore be unsuitable or patient-friendly for ophthalmic applications.
Provided are iodine compositions that can avoid some of the drawbacks of the prior art and can be useful as disinfectants or disinfectants, such as in the treatment or prevention of diseases and conditions caused by or associated with microorganisms. That is the object of the present invention. Further objections of the invention will become apparent based on the following description, examples and claims of the invention.

European Patent Application Publication No. 0526695 International Publication No. 2011084473 Pamphlet US Patent Application Publication No. 2012/0219640 International Publication No. 2012/007776 Pamphlet

In a first aspect, the invention relates to a composition comprising a carrier comprising an iodine molecule and an alkane hemifluoride. In some embodiments, the carrier is selected from formula (II): CF ₃ (CF ₂ ) _n- (CH ₂ ) _m CH ₃ (where n and m are each independently selected from an integer of 3-10, respectively. Includes alkane hemifluoride. In another aspect, the composition may be essentially water-free.

In a further aspect, the invention comprises an iodine molecule and an alkane hemifluoride for use as a pharmaceutical, preferably a pharmaceutical for the treatment or prevention of a disease or condition of skin or mucosal tissue, or eye or eye tissue. A composition comprising a carrier is provided, preferably the disease or condition is associated with or caused by the microorganism.

The present invention relates to a composition comprising a carrier containing an iodine molecule and an alkane hemifluoride.

The iodine molecule, sometimes referred to as elemental iodine, is a metallic gray / dark solid with a chemical formula of I ₂ and a molecular weight of 253.81 g / mol. Iodine molecules have been found to be effective in destroying microorganisms such as bacteria, fungi, Demodex and viruses or inhibiting their growth / proliferation.

The carrier of the composition according to the invention acts as a carrier for the iodine molecule and can be in liquid, semi-solid or solid form. Preferably, the iodine molecule is dissolved in the carrier and / or is completely miscible, i.e., the compositions of the invention are preferably in the form of any particles or at room temperature conditions, ie 15-25 ° C. It also does not contain solid phase iodine.

In one preferred embodiment, the carrier is a liquid. Preferably, the iodine molecule dissolves in a liquid carrier to form a clear solution. As understood herein, terms such as "clear solution" or "solution" refer to a liquid solution in which all solutes are completely soluble or soluble under room temperature conditions, ie 15-25 ° C. The resulting solution does not contain any particulate or solid phase components. In the present invention, the iodine molecule is preferably completely dissolved in a liquid carrier containing alkane hemifluoride, which may provide a clear, purple-pink solution, depending on the degree of dilution.

The composition according to the invention comprises an alkane hemifluoride (sometimes abbreviated as SFA), wherein the alkane hemifluoride has at least one total fluoride segment (F-segment) and at least one non-futh. It can be defined as a linear or branched chain compound composed of a hydrocarbon segment (H-segment). Preferably, the alkane hemifluoride is a linear compound composed of one total fluoride segment (F-segment) and one non-fluorinated hydrocarbon segment (H-segment). In the branched alkanes of hemifluoride, the alkanes of hemifluoride may contain branched non-fluorinated hydrocarbon segments, the hydrocarbon segments as substituents of -CH ₃ , -C ₂ H ₅ , ,. Includes one or more of the alkyl groups selected from the group consisting of -C ₃ H ₇ and -C ₄ H ₉ .

In particular, the present invention is a composition comprising a carrier containing an iodine molecule and an alkane hemifluoride, wherein the alkane hemifluoride is of the formula CF ₃ (CF ₂ ) _n —R _m (I).
(In the formula, n is an integer selected from 1 to 12, R is a linear or branched chain alkyl or cycloalkyl having m carbon atoms, and m is from 2 to 12. Is the integer chosen).

In one preferred embodiment, the carrier is an alkane hemifluoride of formula (I) (where n is an integer selected from 3 to 10 and R is a direct chain having m carbon atoms. It is a chain or branched chain alkyl or cycloalkyl, where m is an integer selected from 4-8).

In the above embodiment where R is preferably a branched alkyl, R is any one of the butyl isomers such as isopropyl, isobutyl, sec-butyl, or tert-butyl, neo-pentyl, tert-. From any one of the pentyl isomers such as pentyl, sec-pentyl, isopentyl, or 3-pentyl; from any one of the hexyl or heptyl isomers and, for example, any one of the octyl isomers such as isooctyl. Can be selected.

In another preferred embodiment, the carrier is an alkane hemifluoride of formula (I) (where n is an integer selected from 3 to 10 and R is a direct cell having m carbon atoms. It is a chain alkyl, where m is an integer selected from 4-8).

In an alternative preferred embodiment, the carrier is an alkane hemifluoride of formula (I) (where n is an integer selected from 3 to 10 and R has m carbon atoms. It is a linear alkyl, where m is an integer selected from 2-8).

As understood herein, the term linear alkyl can refer to non-branched and linear alkyl groups. For example, R of formula (I) can preferably be selected from ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, or n-heptyl, and n-octyl.

In another preferred embodiment, the carrier is an alkane hemifluoride of formula (I) (where n is an integer selected from 3 to 10 and R is a cyclo having m carbon atoms. It is alkyl and m is an integer selected from 4-8).

As understood herein, the term cycloalkyl can refer to cyclic, i.e., ring-forming alkyl groups such as cyclobutyl, cyclopentyl or cyclohexyl.

In a preferred embodiment, the alkane hemifluoride featured in the compositions according to the invention is a liquid, i.e. a compound that is present in a liquid state at at least one temperature within the temperature range of 4 ° C to 50 ° C. Preferably, the alkane hemifluoride featured in the compositions according to the invention is a compound that is liquid at room temperature (RT), such as temperatures between 15 ° C and 25 ° C. Alternatively, the alkane hemifluoride, or optionally a mixture of two or more alkane hemifluoride, characterized in the composition, may be semi-solid or solid at room temperature, but at 26 ° C. It has a melting point of at least one temperature in the range of ~ 45 ° C.

In another particularly preferred embodiment, the invention relates to an iodine molecule and formula (II) :.
CF ₃ (CF ₂ ) _n- (CH ₂ ) _m CH ₃ equation (II)
It relates to a composition comprising a carrier containing an alkane hemifluoride (in the formula, n and m are each independently selected from an integer of 3-10).

Preferably, the alkane hemifluoride is CF ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ (F4H5), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₅ CH ₃ (F4H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₅ CH ₃ (F6H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₇ CH It can be selected from ₃ (F4H8), CF ₃ (CF ₂ ) _7- (CH ₂ ) ₇ CH ₃ (F8H8) and CF ₃ (CF ₂ ) _9- (CH ₂ ) ₄ CH ₃ (F10H5). More preferably, the alkane hemifluoride is selected from CF ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ (F4H5) and CF ₃ (CF ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8). Can be done. In another embodiment, the composition may comprise an iodine molecule dissolved in any one of the selected alkane hemifluorides described above.

In another alternative embodiment, the invention is an iodine molecule and formula (II) :.
CF ₃ (CF ₂ ) _n- (CH ₂ ) _m CH ₃ equation (II)
It relates to a composition comprising a carrier containing an alkane hemifluoride (where n is an integer selected from 2-9 and m is an integer 1-7).

The alkane hemifluoride is CF ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ (F4H5), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₅ CH ₃ (F4H6), CF ₃ (CF ₂ ). ) ₅ -CH ₂ CH ₃ (F6H2), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₅ CH ₃ (F6H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₇ CH ₃ (F4H8), CF ₃ (CF ₂ ) _7- (CH ₂ ) ₇ CH ₃ (F8H8) and CF ₃ (CF ₂ ) _9- (CH ₂ ) ₄ It can be selected from CH ₃ (F10H5). More preferably, the alkane hemifluoride is CF ₃ (CF ₂ ) ₅ -CH ₂ CH ₃ (F6H2), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ (F4H5) and CF ₃ (CF). ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8) can be selected. In another embodiment, the composition may comprise an iodine molecule dissolved in any one of the selected alkane hemifluorides described above.

In another particularly preferred embodiment, the invention relates to an iodine molecule and formula (II) :.
CF ₃ (CF ₂ ) _n- (CH ₂ ) _m CH ₃ equation (II)
Concerning a composition comprising a carrier containing an alkane hemifluoride (where n and m are each independently selected from an integer of 3-10) and the composition is essentially water free. .. In such embodiments, preferably the alkane hemifluoride is CF ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ (F4H5), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₅ CH ₃ (F4H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₅ CH ₃ (F6H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₇ CH ₃ (F4H8), CF ₃ (CF ₂ ) _7- (CH ₂ ) ₇ CH ₃ (F8H8) and CF ₃ (CF ₂ ) _9- (CH ₂ ) ₄ CH ₃ (F10H5) Can be done.

Moreover, in a further embodiment, the present invention relates to an iodine molecule and formula (II) :.
CF ₃ (CF ₂ ) _n- (CH ₂ ) _m CH ₃ equation (II)
It comprises a carrier containing an alkane hemifluoride (where n is an integer selected from 2-9 and m is an integer 1-7), and the composition essentially contains water. Not included, with respect to the composition. In such embodiments, preferably the alkane hemifluoride is CF ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ (F4H5), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₅ CH ₃ (F4H6), CF ₃ (CF ₂ ) ₅ -CH ₂ CH ₃ (F6H2), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₅ CH ₃ (F6H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ) ₇ CH ₃ (F6H8), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₇ CH ₃ (F4H8), CF ₃ (CF ₂ ) _7- (CH ₂ ) ₇ CH ₃ (F8H8) and CF ₃ (CF) ₂ ) _9- (CH ₂ ) ₄ CH ₃ (F10H5) can be selected.

An alternative academic term for a particular hemifluorinated alkane described in parentheses above and which may be used herein is the general formula F _{n Hm} (where F is a linear total fluoride. It means a hydrocarbon segment, H means a linear non-fluorinated hydrocarbon segment, and n and m are the number of carbon atoms in each segment). For example, F4H5 is 1-perfluorobutylpentane or CF ₃ (CF ₂ ) _3- (CH ₃ ) ₄ CH ₃ (formula F (CF ₂ ) ₄ (CH ₂ ) ₅ H, or is represented as such formula. Can be used to represent), which is a linear total fluorinated segment F with 4 carbons (n = 4) and a direct with 5 carbons (m = 5). It has a chain of non-fluorinated hydrocarbon segments.

Most preferably, the compositions of the present invention include iodine molecules and F (CF ₂ ) ₆ (CH ₂ ) ₂ H (F6H2), F (CF ₂ ) ₄ (CH ₂ ) ₅ H (F4H5) and F (CF ₂ ). ) _{6 (} CH ₂ ) Contains a liquid carrier comprising or consisting of an alkane hemifluoride selected from 8H (F6H8). A particular preferred alkane _hemifluoride F6H2 having the chemical formula F (CF ₂ ) ₆ (CH ₂ ) 2H, also known as perfluorohexyl-ethane, is a chemically and physiologically inert, water-insoluble solution. It has a density of 1.57 g / cm ³ at 20 ° C and a refractive index of 1.295 at 20 ° C. A particular preferred alkane hemifluoride F4H5 having the chemical formula F (CF2) 4 (CH2) 5H, also known as 1-perfluorobutyl-pentane, is a chemically and physiologically inert, water-insoluble solution. It has a density of 1.284 g / cm ³ at 25 ° C and a refractive index of 1.3204 at 20 ° C. A particularly preferred alkane hemifluoride F6H8 contained in the liquid carrier of the composition of the invention, also known as 1-perfluorohexyl-octane, is also a chemically and physiologically inert, water-insoluble liquid. It has a density of 1.35 g / cm ³ at 25 ° C and a refractive index of 1.3432 at 20 ° C. In a preferred embodiment, the composition may be substantially free of water.

The carrier of the composition of the invention comprising an alkane hemifluorinate (“a” semifluorinated alkane) is at least one alkane hemifluoride, preferably of formula (I) or formula (II) or any of the other formulas described above. It should be understood herein to include either. Optionally, however, the carrier of the composition is an alkane of the formula (I) or formula (II) of more than one, eg, two or more mixtures, or the half described above. It may contain any one of the alkane fluoride species.

In a further embodiment, the carrier of the composition may consist of any one of the alkanes of formula (I) or formula (II) or the alkanes of hemifluoride specified above. In this context,'a'semifluorinated alkanes should be understood as at least one alkane hemifluoride, but there is also a choice of more than one or more alkane hemifluoride compounds. Can include. Thus, in one embodiment, the carrier of the composition comprises more than one formula (I) or formula (II) hemifluorinated alkane or any one of the hemifluorinated alkanes specified above. Can be. Preferably, the alkane hemifluoride (or optionally a mixture of two or more alkane hemifluorides) is present as a carrier for the iodine molecule and functionally characterized in the composition. It is said that. In an optional embodiment, the composition, however, may include additional active ingredients and / or one or more excipients. In one embodiment of the invention, the composition comprises a carrier consisting of an alkane hemifluoride or a mixture of alkane hemifluorides as defined and optionally one or more excipients or co-solvents. May have.

In a preferred embodiment, the composition of the invention may consist of a carrier comprising an iodine molecule, and optionally an additional active ingredient, and an alkane hemifluoride. In a further preferred embodiment, the composition comprises an iodine molecule, and optionally additional active ingredients, as well as one or more alkane hemifluorides and optionally one or more non-polar cosolvents or excipients. It may consist of a carrier made of. Optionally, the composition may consist of a carrier consisting of an iodine molecule and one or more alkane hemifluorides. Optionally, the composition may consist of a carrier consisting of an iodine molecule and an alkane hemifluoride.

In one embodiment, the invention comprises a carrier consisting of a) an iodine molecule and optionally an additional active ingredient, and b) an alkane hemifluoride and optionally a non-polar cosolvent or excipient. Alkane hemifluoride is the formula (I) CF ₃ (CF ₂ ) _n −R _m (in the formula, n is an integer selected from 1 to 12, and R is m carbon atoms. It is a linear or branched alkyl or cycloalkyl having, and m is an integer selected from 2 to 12), which is an alkane hemifluoride.

In another embodiment, the invention comprises a carrier consisting of a) an iodine molecule and optionally an additional active ingredient, and b) an alkane hemifluoride and optionally a non-polar cosolvent or excipient. The alkane hemifluoride is the formula (I) CF ₃ (CF ₂ ) _n −R _m (where n is an integer selected from 2 to 12 and R is m carbon atoms. It is a linear or branched alkyl or cycloalkyl having, and m is an integer selected from 2 to 12), which is an alkane hemifluoride.

As used herein, the term "consists" and the associated term "consisting" or "consisting" other than those following the term. It is understood to mean that there are no other features. In the context of the composition, if any other component or component is present in the composition other than those following such terms, it does not confer any technical advantage or relevance with respect to the object of the invention. It is present only in trace or residual amounts such as, which is further due to the term "essentially" or "substantially" used in combination with these terms (eg, "becomes essential"). Can be understood. In contrast, the term "comprising" or the associated term "comprises" or "comprising" in the context of a composition has other features other than those following that term. Is understood to mean that can be present in the composition.

In an alternative aspect of the invention, the composition of the invention may comprise a carrier comprising an iodine molecule (I ₂ ) and perfluorocarbon. As understood herein, a perfluorocarbon is a hydrocarbon compound in which all hydrogen atoms have been replaced by another atom, i.e., predominantly or entirely fluorine atoms. Preferably, the perfluorocarbon or total fluoride hydrocarbon has 5-12 carbon atoms. Preferably, the perfluorocarbon is a liquid at room temperature. In another embodiment, the perfluorocarbon can be a compound of formula F (CF ₂ ) _n F (where n is an integer selected from 5-12). Particularly preferred perfluorocarbons are perfluorooctane and perfluorodecalin. Optionally, the composition may also comprise an alkane hemifluoride, preferably an alkane hemifluoride of the above formula (I) or formula (II).

Preferably, when used in therapeutic or prophylactic applications, the amount of iodine incorporated into the composition according to the invention is present in an amount effective to inhibit or prevent the growth and / or proliferation of microorganisms. In another aspect, the iodine molecule is preferably to produce the desired pharmacological effect, such as the pharmacological effect in the treatment of any one of the conditions or diseases as described in more detail below. It can be incorporated into the composition in useful amounts.

In one aspect, the compositions of the invention as described in any of the above embodiments are less than 1 mg / mL, or preferably 0.9 mg / mL, 0.8 mg / mL, 0.6 mg / mL. , 0.5 mg / mL, 0.4 mg / mL, 0.2 mg / mL, 0.1 mg / mL, 0.05 mg / mL, 0.01 mg / mL or less than 0.001 mg / mL of iodine molecules ..

In one embodiment, the composition of the invention may contain less than 1 mg / mL iodine molecules dissolved in the carrier.

In another embodiment, the compositions of the invention are in a carrier, preferably an alkane hemifluoride as defined in any one of the above embodiments and optionally compatible, eg, non-polar. 0.001 mg / mL to 1 mg / mL, or 0.001 mg / mL to 0.9 mg / mL, 0.8 mg / mL, 0.6 mg, dissolved in a carrier containing or consisting of a co-solvent or excipient. Amount of iodine up to one of the values / mL, 0.5 mg / mL, 0.4 mg / mL, 0.2 mg / mL, 0.1 mg / mL, 0.05 mg / mL, 0.01 mg / mL It can contain or consist of molecules.

In one embodiment, the composition is dissolved in a carrier, less than 1 mg / mL, or preferably 0.9 mg / mL, 0.8 mg / mL, 0.6 mg / mL, 0.5 mg / mL, 0. It may contain less than 4 mg / mL, 0.2 mg / mL, 0.1 mg / mL, 0.05 mg / mL, 0.01 mg / mL or 0.001 mg / mL iodine molecules. In embodiments where the carrier may consist solely of alkane hemifluoride, the composition is less than 1 mg / mL, or 0.9 mg / mL, 0.8 mg / mL, dissolved in the alkane hemifluoride carrier. Iodine less than 0.6 mg / mL, 0.5 mg / mL, 0.4 mg / mL, 0.2 mg / mL, 0.1 mg / mL, 0.05 mg / mL, 0.01 mg / mL or 0.001 mg / mL May contain molecules.

In another embodiment where the carrier may consist solely of alkane hemifluoride and optionally non-polar and / or aprotic solvents, or excipients alone, the composition is alkane hemifluoride and optionally. Less than 1 mg / mL or 0.9 mg / mL, 0.8 mg / mL, 0.6 mg / mL, 0.5 mg / mL, 0.4 mg / mL, 0.2 mg / mL dissolved in the carrier containing the co-solvent. It may contain less than mL, 0.1 mg / mL, 0.05 mg / mL, 0.01 mg / mL or 0.001 mg / mL iodine molecules. Preferably, such compositions are non-colorable and / or stable at room temperature for at least 30, 90 or 180 days.

According to one aspect of the invention, the composition may comprise a carrier comprising an iodine molecule and an alkane hemifluoride as described in any of the above embodiments, which further comprises a co-solvent. ..

As understood herein, cosolvents are intended to enhance or solubilize the solubility of iodine molecules and / or any other solid or immiscible component featured in the compositions of the invention. It is a suitable compound. The solid or immiscible ingredient can be, for example, an additional active ingredient or another excipient. Preferably, the co-solvent component of the composition is a liquid that is completely miscible with the alkane hemifluoride, i.e. it mixes with the alkane hemifluoride to form a coherent and single phase, iodine molecule and / Or act as a carrier or carrier for any other ingredient such as an additional active ingredient or additional excipient. The co-solvent is preferably a liquid organic compound that is physiologically tolerated and safe for direct topical administration to the eye, eye tissue and / or skin, dermis, or mucosal tissue.

Preferably, the co-solvent is a non-polar solvent. The non-polar solvent may be non-ionizable and / or aprotonic, preferably such a co-solvent does not support the formation of an iodine ion or iodine oxide species, preferably the co-solvent is: : A solvent that does not support the formation of any one (or combination) of iodine (I-), triiodide (I _{3-), iodine (IO 3-} ⁾ _, ^{or hypoiodate (} IO-).

Saturated hydrocarbons, preferably C1-C10 alkanes (eg, n-pentane, n-hexane, n-heptane, or n-octane); mineral oil; paraffin; siloxane; and one or a mixture of perfluorocarbons. Non-polar solvents are particularly preferred as co-solvents. In a further embodiment, the non-polar solvent can also be selected from saturated, non-branched or branched hydrocarbons with longer carbon chains such as C10-C30, or C10-C40.

In certain preferred embodiments, the co-solvent is a solvent that does not support the formation of iodine ions or iodine oxide species, preferably such co-solvents do not support the formation of iodine ions or iodine oxide species and are preferred. The co-solvent does not support the formation of any one (or combination) of iodine (I-), triiodide (I _{3-), iodine (IO 3-} ⁾ _, ^{or hypoiodate} (IO-) ^: It is a solvent.

The co-solvent may be characterized in the composition according to the invention in an amount of about 38% by weight or less based on the total weight of the carrier. In a further embodiment, the amount of co-solvent is 30% (w / w), 25% (w / w), 15% (w / w) or 10% (w / w), based on the total amount of carrier. Alternatively, the amount can be 5% (w / w) 2% (w / w), or about 1.0% (w / w) or less.

In a further embodiment, the cosolvent is 0.001-5% (w / w), or 0.001-2% (w / w), or 0.01-1% (w / w), based on the total weight of the carrier. It may be characterized by an amount in the range of w / w) or 0.1-1% (w / w).

In an alternative embodiment, the co-solvent may be selected from alcohol. A co-solvent as an alcohol selected from any one or mixture of ethanol, methanol, propanol, or isopropanol or any alcohol physiologically tolerated by the eye or skin. The co-solvent can be an absolute / anhydrous form of alcohol, such as absolute ethanol, methanol, propanol, or isopropanol.

In one embodiment, the co-solvent is ethanol, which is 30% (w / w), 25% (w / w), 15% (w / w) or 10% (w / w) relative to the amount of carrier in the composition. It is characterized by an amount of w), or 5% (w / w) 2% (w / w), or about 1.0% (w / w) or less, and optionally, the carrier is semi-fluffy. Consists of alkanes and ethanol only; and optionally, ethanol is anhydrous. The composition is at least 0.25 mg / ml, at least 0.5 mg / ml, at least 1 mg / mL, at least 1.5 mg / mL, at least 2.0 mg / mL, at least 2.0 mg / mL, dissolved in an alkane hemifluoride and ethanol carrier. It may contain 2.5 mg / mL, at least 3.0 mg / mL or at least 5.0 mg / mL of iodine molecules.

Compositions with particularly higher concentrations of iodine can be useful and advantageous for bactericidal applications, such as disinfection of inanimate surfaces such as surfaces of surgical instruments, machines or means.

In one aspect of the invention, the composition according to the invention may contain up to about 20 mg / ml of iodine molecules. In such embodiments, the composition is at least 1 mg / mL, or at least 1.5 mg / mL, or at least 2.0 mg / mL, or at least 2.5 mg / mL, at least 3.0 mg / mL, at least 5. It may contain 0 mg / mL, at least 10.0 mg / mL or at least 15.0 mg / mL of iodine molecules.

In one embodiment, the composition may contain up to 20 mg / mL of iodine molecules dissolved in the carrier. The composition is at least 1 mg / mL, or at least 1.5 mg / mL, or at least 2.0 mg / mL, or at least 2.5 mg / mL, at least 3.0 mg / mL, at least 5.0 mg / mL, at least 10. It may contain iodine molecules dissolved in a carrier in an amount of 0 mg / mL or at least 15.0 mg / mL. In embodiments where the carrier may consist solely of alkane hemifluoride and optionally the co-solvent, the composition is at least 1 mg / mg dissolved in the carrier consisting of alkane hemifluoride and the optional co-solvent. mL, at least 1.5 mg / mL, at least 2.0 mg / mL, at least 2.5 mg / mL, at least 3.0 mg / mL or at least 5.0 mg / mL, or at least 10.0 mg / mL or at least 15.0 mg / May contain in mL amount of iodine molecules.

In a further embodiment of the invention relating to a composition comprising an iodine molecule and a carrier comprising an alkane hemifluoride as defined in any of the preceding embodiments above, the carrier is preferably the total weight of the carrier. It comprises at least 60% (w / w) amount of alkane hemifluoride or optionally a mixture of alkane hemifluoride. In other embodiments, the carrier is at least 70% (w / w), 75% (w / w), 85% (w / w), 90% (w / w), based on the total weight of the carrier. It may contain 95% (w / w), 98% or at least 99% (w / w) alkane hemifluoride or a mixture of alkane hemifluoride.

In one preferred embodiment, the carrier of the composition according to the invention is a 100% (w / w) alkane hemifluoride or a mixture of alkane hemifluoride. In another embodiment, the carrier comprises an amount of at least 60% (w / w) of alkane hemifluoride or optionally a mixture of alkane hemifluoride based on the total weight of the carrier. In another embodiment, the carrier is at least 70% (w / w), 75% (w / w), 85% (w / w), 90% (w / w), 95% based on the total weight of the carrier. From% (w / w), 98% or at least 99% (w / w) of alkane hemifluoride or a mixture of alkane hemifluoride, and co-solvents or excipients, preferably non-polar co-solvents or excipients. Can be.

As used herein, the term "% (w / w)" is used as a weight percentage of the total weight of the composition (eg, the composition of the carrier) (eg, the total weight of the carrier), unless otherwise indicated. It refers to the amount of components of an object, and "w" represents the weight. For example, the carrier of the composition according to the invention may contain up to about 1.5% (w / w) of co-solvent, such as ethanol, based on the total weight of the carrier. Similarly, unless indicated, the term "% (w / v)" refers to the amount of a component of a composition as a weight percentage of the total volume of the composition (where "w" stands for weight and "v" stands for weight). Represents volume).

In a further embodiment, the composition of the invention is a rapidly evaporating formulation. The composition preferably has an antibacterial effect (eg, against any one or combination of bacteria, fungi, viruses). Preferably, the rapidly evaporating formulation is within 5 minutes, preferably within 3 minutes, more preferably from the time of topical application to a surface, eg, a tissue surface, or any eye surface, or alternative, an inanimate surface. Evaporates within 1 minute. Preferably, such a rapidly evaporating formulation comprises, and even more preferably, iodine molecules dissolved in a carrier comprising or consisting of an alkane hemifluoride characterized by a boiling point below 140 ° C. The rapidly evaporating formulation comprises iodine molecules dissolved in a carrier containing an alkane hemifluoride selected from the group consisting of F6H2 or F4H5. In one embodiment, such a rapidly evaporating formulation comprises or consists of up to 0.5 mg / ml iodine molecules dissolved in F6H2.

In another embodiment, the composition according to the invention may further comprise the active ingredient dissolved in the carrier. Preferably, the active ingredient is present in a therapeutically effective amount, where the therapeutically effective amount, when used herein, is the desired pharmacological effect, more specifically described below. It is meant to be a dose, concentration or intensity useful for producing a pharmacological effect in the treatment of any one of the conditions or diseases as described.

Preferably, the active ingredient is selected from the group consisting of antibiotics, anti-inflammatory agents, analgesics, anesthetics, antiallergic agents, and immunosuppressive agents. The active ingredient can also be selected from corticosteroids. Preferably, the active ingredient is suitable for compounding with an iodine molecule.

Preferred antibiotics are fluoroquinolone (cyprofloxacin, levofloxacin, offloxacin, moxifloxacin, gatifloxacin, etc.); aminoglycoside (tobramycin, gentamycin, neomycin, etc.); polymyxin B combination (polymyxin B / trimetoprim, police, etc.). Examples include poline polymyxin B / bacitracin, neosporin polymyxin B / neomycin / glamicidin, etc.) and other antibiotics (azithromycin, ilotycin, erythromycin, bacitracin, etc.).

Preferred anti-inflammatory agents include corticosteroids (eg, dexamethasone, prednisolone, rotepredonor, difluprednate, fluoromethalone, limexolone, medrisone, hydrocortisone) or NSAIDs (eg, bromfenac, nepafenac, diclofenac, flurubinac). Fen, sprofen, selecoxib, naproxen, rofecoxib).

Preferred anesthetics include proparacaine, lidocaine, tetracaine, benzocaine, butamben, dibucaine, oxybuprocaine, pramocaine, proximethocaine.

Preferred antiallergic agents include pheniramine malleate, epinastine, emedastine, azelastine, olopatadine, ketotifen, pemirolast, nedocromil, rhodoxamide, chromolin.

Preferred immunosuppressants (Preferrred immunosuppressants) include cyclosporine A, tacrolimus, and sirolimus.

An example of a preferred corticosteroid is dexamethasone.

In one embodiment, the invention comprises a) an iodine molecule and additional active ingredients as defined above, and b) a carrier consisting of an alkane hemifluoride and optionally a non-polar co-solvent or excipient. In the composition, the alkane hemifluoride is CF ₃ (CF ₂ ) _n −R _m (in the formula, n is an integer selected from 1 to 12 and R is m carbon atoms. Provided are compositions which are linear or branched alkyl or cycloalkyl having, where m is an integer selected from 2 to 12), which is an alkane hemifluoride.

In another embodiment, the invention consists of a) an iodine molecule and additional active ingredients as defined above, and b) a carrier consisting of an alkane hemifluoride and optionally a non-polar cosolvent or excipient. Alkane hemifluoride is CF ₃ (CF ₂ ) _n −R _m (in the formula, n is an integer selected from 2 to 12 and R is m carbon atoms. Provided is a composition which is a linear or branched alkyl or cycloalkyl having a, m is an integer selected from 2 to 12), which is an alkane hemifluoride.

Optionally, the compositions of the invention may also contain one or more additional excipients as additional ingredients. As used herein, the term "excipient" is more specific to the compositions of the invention to enhance or otherwise modify the physical or chemical composition or stability or therapeutic properties. In particular, it refers to any pharmaceutically acceptable natural or synthetic substance that can be added to the carrier of the composition.

Ingredients of a compound or composition considered as an excipient may also fall within the definition of co-solvent as defined above. In one embodiment, the excipient featured in the compositions of the invention is an excipient that does not support the formation of iodine ions or iodine oxide species, preferably said excipients: iodide ( It does not support the formation of any one (or combination) of I- ⁾ , triiodide (I _{3-), iodine (IO 3-} ⁾ _, ^{or hypoiodate} (IO-).

The compositions of the invention are optionally such as, for example, antioxidants, preservatives, lipid or oily excipients, surfactants or lubricants or combinations of at least two of these excipients. It may contain one or more excipients.

Lipid or oily excipients for use in the compositions of the invention are, for example, triglyceride oils (ie, soybean oil, olive oil, sesame oil, cottonseed oil, castor oil, sweet pepper oil), triglycerides, mineral oils (ie, vaseline and). Liquid paraffin), medium chain triglycerides (MCT), oily fatty acids, isopropyl myristate, oily aliphatic alcohols, sorbitol and fatty acid esters, oily sucrose esters, or any other oily tolerated by the eyes or skin. May contain substances. The lipid or oily excipient may also serve as a co-solvent for iodine molecules according to the purpose of the co-solvent as defined above.

In one embodiment, the amount of excipient featured in the composition according to the invention is 30% (w / w), 25% (w / w), 15% (w / w /) relative to the total weight of the carrier. It can be an amount of w) or 10% (w / w), or 5% (w / w) 2% (w / w), or about 1.0% (w / w) or less.

Preferably, the composition of the invention is substantially free of water. As understood herein, the term "substantially free" or, alternative, "essentially free" with respect to a component of a composition is the presence or absence of such component in trace amounts or less. When present in trace amounts, the component means that it does not provide any technical contribution to the composition.

In a preferred embodiment of the invention, the composition is essentially water-free.

In another further preferred embodiment, the composition according to the invention may be substantially free of preservatives and / or surfactants such as antibacterial preservatives. Preferably, the composition is free of, ie, free of any one of the preservatives or surfactants such as water and / or antibacterial preservatives.

Optionally, the compositions according to the invention are substantially free of polymers or complexing agents capable of forming a complex with or binding to iodine molecules such as polyvinylpyrrolidone (PVP) or Cadexomer. Can be.

In another preferred embodiment, the composition according to the invention is an iodine ion or iodine oxide species, preferably: iodide (I ⁻ ), triiodide (I ₃ ⁻ ), iodine (IO ₃ ⁻ ), or hypoyodate. It may be substantially free of iodine ions or iodine oxide species as selected from any one (or combination) of (IO- ⁾ . The species may comprise any suitable counterion or proton form thereof (the of), for example, iodide may have a potassium or sodium counterion (ie, NaI or KI).

In a preferred embodiment, the composition of the invention, preferably a composition that is substantially free of water and / or an iodine ion or iodine species of oxide, preferably: iodide (I ⁻ ), triiodide (I ₃₋ ⁾ . , Iodine ion or iodine oxide species as selected from any one (or combination ⁾ of iodine (IO _3- ⁾ or hypoyodate (IO-) shall be uncolored. It is sexual, preferably non-coloring when administered or contacted with any one of the following surfaces: skin or skin tissue, eye or eye tissue, and optionally any one of the fabrics. As defined herein, the term non-coloring refers to the absence of any persistent discoloration or persistent colored residue on the site or surface to which the composition is topically applied or contacted. When the composition of the invention comprising an iodine molecule and alkane hemifluoride as a carrier is first administered to a site of topical application such as the skin or filter paper surface, some colors will first appear on the surface. That is, although it can be observed immediately after administration, it has been observed that coloration does not persist under ambient or skin surface conditions and no long-term discoloration or residue is observed.

Preferably, any coloring or color present by application of the compositions of the invention disappears or dissipates within 10 minutes, 5 minutes, or preferably 1 minute. Therefore, the color does not subsequently transfer to any surface in contact with the site of administration. Thus, the color does not transfer, for example, to the fabric in contact with the site of iodine administration, which is a great advantage over conventional iodine formulations as aqueous disinfectants or disinfectants.

Although not desired to be bound by theory, the lack of coloration or discoloration observed in the topical application of the composition according to the invention is an iodine ion and / or iodine oxide species such as triiodide (I _3- ⁾ in the composition. We assume that this is due to the absence of such species and the absence of their formation. The reddish brown or yellow color of many aqueous iodine formulations and the corresponding discoloration and coloring of the skin and other surfaces are generally due to such species, especially triiodide. The compositions of the present invention are advantageous in improving patient compliance when the composition is used as a medicine, as skin discoloration or cross-contamination on clothing can be avoided or reduced. obtain.

In another, and optional aspect, the compositions of the invention may be formulated alternative to provide a coloring effect, the composition being a colored or coloring or coloring composition. Can include at least one component species (ie, triyodide (I _3- ⁾ ), excipients or co-solvents. Preferably, the composition is suitable for use in applications where coloring or coloring can be useful as an indicator of the surface compartment to which or contacts the composition, eg, surgery. Examples of colorable compositions include alkane hemifluoride and alcohol co-solvents.

It has also been found that the compositions of the invention appear to be surprisingly highly stable, as well as at relatively high concentrations, even when formulated in lower concentrations of iodine molecules. State-of-the-art compositions, such as those offered for ophthalmic applications, typically have only 0.5% available iodine, ultimately about 2.5 ppm (parts per million) iodine molecules. It is based on an aqueous formulation containing a 5 w / v% povidone iodine complex that provides only as an active species (eg, Minims®, Betazine®).

As described in more detail in the examples below, the compositions of the invention comprising a carrier consisting of alkane hemifluoride and / or perfluorocarbon will precipitate iodine molecules, solids or particles after prolonged storage. Higher concentrations of active iodine molecule formulations can be formulated without causing any physical changes such as the formation of seeds or aggregates from the solution. Compositions based on liquid or solid carriers of co-solvents or excipients that do not lead to the formation of colorating species, such as one or a mixture of alkane hemifluorides, and hydrocarbon compounds are also stable and uncolored. It is observed to be sexual and also to allow formulations of high concentrations of iodine molecules (ie, iodine molecules greater than 100, 250, 500 ppm or up to 1000 ppm).

In the context of therapeutic applications that rely on topical administration to the tissue surface of a patient or subject, preferably a human patient, it is important that the composition can be easily and consistently applied and distributed over the surface. For example, if the tissue surface is skin, or the surface tissue of the eye, the composition also needs to reach, for example, the folds / crevices formed by the tissue with limited direct accessibility. The iodine molecular composition formulated using the carrier based on alkane hemifluoride according to the present invention provides a composition having good extensibility for topical application. Achieving a patient-friendly composition with good sensory properties is also advantageous, for example in achieving patient compliance. The hemifluorinated alkane composition according to the invention provides a pleasing "smooth" sensation when applied, for example, to the eyes or skin.

In a preferred embodiment, the compositions of the invention are stable, preferably at room temperature, for at least 30 days. In a further embodiment, the composition is stable at room temperature for preferably at least 90 days, more preferably at least 180 days.

In a further preferred embodiment, the composition of the invention is stable without protection from light, preferably the composition is stable at room temperature for at least 30 days without protection from light, more preferably at least. It is stable for 90 days, or even more preferably for at least 180 days.

The stability of a composition can be determined by comparing the properties with respect to the properties observed for the composition when initially prepared. Properties that can be used to determine stability include determination of iodine molecule content by analytical methods known in the art (eg, ultraviolet-visible measurements) or other iodine species to determine iodine molecule content. (For example, coloring test, ultraviolet visible measurement). Stability can also be assessed by comparing the overall appearance of the composition for physical changes such as precipitation, particle formation and color changes.

The iodine compositions of the present invention are stable over a wide concentration range of iodine molecules without the need to include many additional excipients and composition components. For example, the compositions of the invention are additional such as buffers or pH regulators, or complexing agents to enhance the solubility of iodine that may be typically required for aqueous compositions containing iodine. Can be prepared without the use of stabilizers.

In another aspect of the invention, the composition may be formulated as any one of a solution, a semi-solid, a cream, a lotion, an ointment, or a swab.

The compositions according to the invention as described in any one of the above embodiments can also be used in therapy as a drug or pharmaceutical.

In certain embodiments, the composition can be used as a disinfectant and / or disinfectant in the treatment or prevention of a disease or condition in a subject in need thereof. Preferably, the compositions of the invention can be used to prevent or inhibit the growth or proliferation of microorganisms.

As used herein, the term "antiseptic" refers to a composition that can prevent or inhibit the growth of microorganisms and / or destroy microorganisms, in particular those that can cause infections or sepsis. Can be synonymous with the term microorganism or killing agent. The term "bactericidal agent" refers to a composition that is topically applied to a subject, more preferably to an inanimate surface to which the subject may come into contact with or may come into contact, to inhibit or prevent the growth of microorganisms and / or destroy the microorganisms. Point to.

As understood herein, the situation of prevention of a disease or condition, or the use of the compositions of the invention in prophylactic treatment, is the occurrence, exarcation, or risk of development of said disease or condition in a subject. Refers to the use of the composition to prevent. For example, subjects with cuts or surface wounds on the skin may optionally use and apply the composition to the cuts or surface wounds on the skin to avoid infection and allow for faster healing thereof. Can destroy microorganisms and / or inhibit their growth and proliferation.

The composition according to any of the above embodiments may be used specifically for the treatment or prevention of the use of a disease or condition affecting the skin or mucosal tissue, the composition being applied to the skin and / or mucosal tissue. Administered topically. As understood herein, the term "dermis" refers to skin tissue, which is the various layers, related tissues or cell layers, ie the dermis (ie, stratum corneum and living). Includes epidermis), dermis or dermis and inferior skin, and all its forms. The composition can be administered on any surface of the subject's skin. Preferably, it is administered to non-damaged or intact skin, such as cuts, lacerations, abrasions, burns, or wounds.

Mucosal tissue refers to tissue containing epithelial cells and connective tissue, preferably mucosal tissue or membrane of the nose, mouth or buccal cavity.

In a further aspect, the composition according to any of the above embodiments may also be used for the treatment or prevention of a disease or condition affecting the eye or eye tissue, the composition being administered topically to the eye or eye tissue. Will be done. Ocular tissue refers to any anatomical aspect of an ocular organ, such as the cornea, or conjunctiva, or meibomian gland, or eyelid margin, or eyelashes.

In a preferred embodiment, the compositions may be administered topically to the surface of the eye and any area or tissue of the eye that may be more accessible by topical administration such as the cornea or conjunctiva, or to the rim or horn of the eyelid.

Preferably, the composition is used to treat or prevent a disease or condition associated with or caused by a microorganism. Preferably, the microorganism is pathogenic, i.e., it can cause disease. Microorganisms can be selected from any one or a combination of bacteria, Demodex, fungi and viruses. Further microorganisms in which the compositions of the invention may optionally be therapeutically useful may be amoeba, or yeast.

Bacteria can include gram-positive or gram-negative species. In a preferred embodiment, the compositions of the invention may be used to treat or prevent a disease or condition associated with or caused by a bacterium, wherein the bacterium is preferably Streptococcus, Staphylo. Genus Staphylococcus, genus Enterococcus, genus Peptostreptococcus, genus Pseudomonas, genus Mycobacteria, genus Mycobacteria, genus Hemophilis ), One or a combination of bacteria from the genus Enterococcus, and the genus Klebsiella.

Viruses include simple herpesvirus (HSV), adenovirus, varicella-zoster virus (VZV), picornavirus, poxvirus, influenza virus and human immunodeficiency virus (HIV).

In one preferred embodiment, the disease or condition is Staphylococcus aureus, pseudomonas aeruginosa, candida albicans, ensis lis s s s s s s s s s s s s s s s s s s s s s s. It is associated with or caused by a microorganism selected from the group consisting of Streptococcus pneumoniae, Proteus mirabilis, and Propionibacterium acnes.

When the composition is intended for use in the treatment or prevention of a disease or condition of the eye or eye tissue, the disease or condition treated is preferably blepharitis, bacterial conjunctivitis, dry eye, follicular conjunctivitis. , Giant papillary conjunctivitis, corneal ulcer, keratitis, neoconjunctivitis, HSV keratitis, ocular allergy, neoplastic conjunctivitis, ulcerative infectious keratitis, epithelial keratitis, interstitial keratitis and epidemic keratitis It is selected from the group of.

In a particularly preferred embodiment, the composition for ocular use has an iodine molecule content of preferably less than 0.5% (w / v), less than 0.1% (w / v). It is formulated as a composition that is less than 0.01% (w / v) or less than 0.001% (w / v).

If the composition is intended for use in the treatment or prevention of a disease or condition of the skin or mucosal tissue, preferably the composition is an intact skin or mucosal tissue, preferably a wound, cut, surgical wound, It can be used to treat intact skin or mucosal tissue selected from burns, abrasions, lacerations, ulcers, rashes, and erosions. In another embodiment, the composition comprises an infection or microbial proliferation at an site where the skin or mucosal tissue is not intact, preferably at the site of a wound, cut, surgical wound, burn, abrasion, laceration, ulcer, rash, or erosion. Can be used to prevent. In a further embodiment, the compositions of the invention can be used to treat or prevent a disease or condition, preferably a contusion, or an infectious disease, preferably a fungal and / or bacterial infection, such as athlete's foot.

In certain preferred embodiments, the composition for use in the treatment of a disease or condition of skin or mucosal tissue has an iodine molecule content of preferably at least 0.01% (w / v). It is formulated as a composition which is at least 0.1% (w / v) and at least 0.5% (w / v).

In a further embodiment of the invention, the composition for therapeutic or prophylactic use may be administered topically to a tissue or organ at any one or more stages before, during, or after surgery or medical procedure. .. In a preferred embodiment, the composition is preoperatively to the tissue or organ prior to surgery, i.e., prior to surgical treatment of said tissue or organ, eg, before cataract surgery, lathic surgery, corneal ablation or intravital injection. Can be administered topically, during, or later (to prevent bacteria present in the cornea or conjunctival from being carried inside the eye).

Described in any one of the above embodiments in the manufacture or preparation of a pharmaceutical agent or drug for the treatment or prophylactic treatment of a subject in need thereof for any one of the diseases or conditions described herein. The use of such compositions is also provided in the context of the present invention.

Also provided within the context of the invention are methods of treating or prophylactically treating a subject having, or potentially suffering from, any one of the diseases or conditions described herein. The method may include topical administration of any one of the defined compositions to said subject. For example, when the composition is administered to the eye, the composition may be instilled directly and locally on the eye or eye tissue.

The therapeutic methods and compositions for therapeutic use further preferably target human subjects, but also veterinary subjects such as mammals such as dogs, cats, horses, or other livestock. Target.

In another aspect, the invention may relate to the use of the composition according to any of the above embodiments in a cosmetological preparation.

In yet another embodiment, the composition according to any of the above embodiments may also be used as a disinfectant or disinfectant, the composition being administered to a biological surface and / or an inanimate surface. In one preferred embodiment, the composition can be used as a disinfectant for inanimate surfaces, preferably surfaces of surgical instruments, machines or means.

In addition, the invention can also provide a kit comprising the composition according to the invention described herein, which requires a suitable container for holding and / or storing the composition. Includes a dispenser suitable for topical administration of the composition to the subject or surface.

The present invention may include the following numbered items:
1. 1. A composition comprising a carrier comprising an iodine molecule and alkane hemifluoride and / or perfluorocarbon.
2. 2. The composition according to item 1, wherein the composition is substantially free of water.
3. 3. The composition according to any one of items 1 or 2, wherein the perfluorocarbon compound is a total fluoride hydrocarbon having 5 to 12 carbon atoms.
4. The composition according to any of the preceding items, wherein the perfluorocarbon is a compound of the formula F (CF ₂ ) _n F (where n is an integer selected from 5 to 12).
5. The composition according to any of the preceding items, wherein the perfluorocarbon is selected from perfluorooctane, or perfluorodecalin, and perfluorooctylbromid.
6. The alkane hemifluoride has the formula (I) :.
CF ₃ (CF ₂ ) _n −R _m formula (I)
(In the formula, n is an integer selected from 1 to 12, R is a linear or branched-chain alkyl, or a cycloalkyl having m carbon atoms, and m is 2 to 12. The composition according to any one of the preceding items, which is an alkane hemifluoride (which is an integer selected from).
7. The alkane hemifluoride has the formula (II) :.
CF ₃ (CF ₂ ) _n- (CH ₂ ) _m CH ₃ equation (II)
The composition according to item 6, which is an alkane hemifluoride (where n and m are each independently selected from an integer of 3 to 10 in the formula).
8. Item 7. The composition according to item 7, wherein the alkane hemifluoride is selected from F4H5, F4H6, F4H8, F6H6, F6H8, F8H8 and F10H5, preferably from F4H5 and F6H8.
9. The composition according to any one of the preceding items, wherein the iodine molecule is dissolved in the carrier.
10. The amount of iodine molecules dissolved in the carrier is 1 mg / mL, 0.8 mg / mL, 0.6 mg / mL, 0.5 mg / mL, 0.2 mg / mL, 0.1 mg / mL, 0.05 mg / mL. The composition according to any one of the preceding items, which is less than mL, 0.02 mg / mL, 0.01 mg / mL, or 0.001 mg / mL.
11. The composition is free of iodine seeds from the group consisting of any one or combination of iodide (I ⁻ ), triiodate (I ₃ ⁻ ), iodine (IO _3- ), or ^hypoiodate (IO ⁻ ). , The composition according to any one of the preceding items.
12. The composition further comprises an active ingredient dissolved in the carrier, which optionally comprises an antibiotic, an anti-inflammatory agent, an analgesic, an anesthetic, an immunosuppressive agent, and an antiallergic agent. The composition according to any one of the preceding items, selected from the group.
13. The composition according to any one of the preceding items, wherein the carrier further comprises a co-solvent, wherein the co-solvent is preferably selected from an alcohol, or a non-polar solvent or a mixture thereof.
14. The co-solvent is a solvent that does not support the formation of iodine ions or iodine oxide species, preferably the co-solvent is iodide (I ⁻ ), triiodide (I ₃ ⁻ ), iododate (IO ₃ ⁻ ), or hypo. The composition according to any one of the preceding items, which is a solvent that does not support the formation of any one or combination of iodine (IO- ⁾ .
15. Item 13 or 14, wherein the co-solvent is a non-protic solvent selected from one or a mixture of saturated hydrocarbons or alkanes such as pentane, hexane, heptane, or octane; mineral oil, paraffin, and siloxane. The composition described.
16. The composition according to item 13 or 14, wherein the co-solvent is an alcohol selected from any one or a mixture of ethanol, methanol or isopropanol, preferably absolute ethanol, methanol or isopropanol.
17. The composition according to any one of items 13 to 16, wherein the carrier contains the co-solvent in an amount of up to about 38% by weight based on the total weight of the carrier.
18. The composition according to any one of the preceding items, wherein the carrier comprises alkane hemifluoride and / or perfluorocarbon.
19. The composition according to any one of the preceding items, wherein the amount of iodine molecules dissolved in the composition or carrier is at least 1 mg / mL or up to 20 mg / mL.
20. The composition according to any one of the preceding items, wherein the composition comprises an iodine molecule and a carrier consisting of at least one alkane hemifluoride and / or perfluorocarbon.
21. The composition comprises an iodine molecule and the carrier, and optionally an active ingredient, and optionally a co-solvent, such as ethanol, or an excipient, wherein the carrier comprises an alkane hemifluoride and. / Or the composition according to any one of the preceding items, comprising perfluorocarbon.
22. The composition according to any one of the preceding items, wherein the composition comprises an iodine molecule and a carrier consisting of an alkane hemifluoride and / or a perfluorocarbon.
23. To any one of the preceding items, which is non-coloring when the composition is applied to any one of the surface or tissue; preferably skin, mucosal tissue, eye or eye tissue, or fabric. The composition described.
24. The composition is stable for at least 30 days, preferably for at least 90 days, more preferably for at least 180 days, and optionally the composition is stable without protection from light. , The composition according to any one of the preceding items.
25. 24. The composition of item 24, wherein the composition is stable at room temperature (15-25 ° C.).
26. The composition according to any one of the preceding claims, wherein the composition is formulated as a liquid, semi-solid, cream, lotion, ointment, or swab.
27. The composition according to any one of the preceding items for use as a drug.
28. The composition according to any one of the preceding items for use as a disinfectant and / or a disinfectant.
29. 27-28. The composition according to item 27-28, which is intended for use in the treatment or prevention of a disease or condition affecting the skin or mucosal tissue, wherein the composition is locally administered to the organ or tissue.
30. 27-29, wherein the composition is for use in the treatment or prevention of a disease or condition affecting the eye or eye tissue and the composition is administered topically to the eye or eye tissue. Composition.
31. The composition for use according to any one of items 27-30, wherein the disease or condition is associated with or caused by a microorganism.
32. 31. The composition for use according to item 31, wherein the microorganism is selected from any one or combination of bacteria, Demodex, fungi, yeasts or viruses.
33. The disease or condition is associated with or caused by a microorganism, the microorganism being Staphylococcus aureus, Pseudomonas erginosa, Candida albicans, Aspergillus brushliensis, Streptococcus pneumoniae, Proteus Mirabilis, The composition for use according to any one of items 27-32, selected from any one or combination of the group consisting of Propionibacterium acnes.
34. In treating or preventing a disease or condition of skin or mucosal tissue, preferably a disease or condition selected from wounds, cuts, abrasions, burns, surgical site wounds, ulcers, erosions, contusions, and infectious diseases. The composition for use according to any one of items 27-33, which is intended for use.
35. The composition comprises a disease or condition of the eye or eye tissue, preferably eyelid inflammation, bacterial conjunctivitis, dry eye, follicular conjunctivitis, giant papillary conjunctivitis, corneal ulcer, keratitis, conjunctivitis neoplasia, HSV conjunctivitis. For use in the treatment or prevention of diseases or conditions selected from the group consisting of eye allergies, ulcerative infectious keratitis, epithelial keratitis, interstitial keratitis, epidemic keratoconjunctivitis, and neoplastic conjunctivitis. 27. The composition for use according to item 27-33.
36. Any of items 27-35, wherein the therapeutic or prophylactic use comprises topically administering the composition to a tissue at any one step or combination prior to, during, or after surgery or medical procedure. The composition for use according to one.
37. 36. The composition for use according to item 36, wherein the surgery or medical procedure is an ophthalmic procedure, preferably cataract surgery, LASIK, corneal ablation, or intravitreal injection.
38. A method of treating or preventing a disease or condition associated with or caused by a microorganism, wherein the microorganism is preferably selected from any one or a combination of bacteria, genus Acne, fungi, or viruses. The method is to locally administer the composition according to any one of items 1 to 26, preferably to the skin or mucous tissue (muscosal virus) of the subject, or the eye or eye tissue in need thereof. Contains, preferably any one of the above composition is a) before, b), or c) after surgery or medical treatment, preferably to inhibit or prevent infection or microbial growth and optionally. A method of administration in two stages or combinations.
39. The use of the composition according to any one of items 1-26 in the manufacture of a pharmaceutical for use in the treatment of a disease or condition associated with or caused by a microorganism, wherein the microorganism is preferred. Selected from any one or combination of bacteria, Demodex, fungi, or viruses; preferably, the drug is administered topically to a subject and / or to the subject's skin, mucosal, eye or eye tissue. Suitable for topical administration of, use.
40. Use of the composition according to any one of items 1-26 as a disinfectant or disinfectant, preferably the composition being administered to a biological surface and / or an inanimate surface.
41. The use of the composition according to any one of items 1-26 as a disinfectant for an inanimate surface, preferably the inanimate surface being the surface of a surgical instrument or means.
42. Use of the composition according to any one of items 1-26 in a cosmetological preparation.
43. A kit comprising the composition according to any one of items 1-26, wherein the kit is in a container suitable for holding and / or storing the composition and the subject or surface in which it is required. A kit containing a dispenser suitable for topical administration of the composition.
44. The composition is a carrier consisting of 1-perfluorohexyl-octane or 1-perfluorobutyl-pentane, which is optionally dissolved in the carrier containing a non-polar solvent. The composition according to any one of items 6 to 24, which comprises an iodine molecule of about 1.0 mg / mL.
45. Item 6 wherein the composition is a carrier comprising or consisting of perfluorohexyl-ethane and optionally comprises up to about 0.5 mg / mL iodine molecules dissolved in the carrier comprising a non-polar solvent. The composition according to any one of 24 to 24.

The invention may also include:
1.1 a) Iodine molecule, and b) a carrier containing an alkane hemifluoride, wherein the alkane hemifluoride is of formula (I) :.
CF ₃ (CF ₂ ) _n −R _m formula (I)
(In the formula, n is an integer selected from 1 to 12, R is a linear or branched chain alkyl or cycloalkyl having m carbon atoms, and m is from 2 to 12. Alkane hemifluoride (which is the integer of choice),
Composition.
1.2 a) It consists of a carrier consisting of an iodine molecule and optionally an additional active ingredient, and b) an alkane hemifluoride and optionally a non-polar co-solvent or excipient, wherein the alkane hemifluoride is of the formula. (I):
CF ₃ (CF ₂ ) _n −R _m formula (I)
(In the formula, n is an integer selected from 1 to 12, R is a linear or branched chain alkyl or cycloalkyl having m carbon atoms, and m is from 2 to 12. Alkane hemifluoride (which is the integer of choice),
Composition.
1.3 The composition according to any one of the preceding items, wherein the iodine molecule is dissolved in the carrier in an amount of up to about 20 mg / mL (anamount).
1.4 Any of the preceding items, wherein the iodine molecule is dissolved in the carrier up to about 1 mg / mL, optionally in an amount in the range of about 0.001 mg / mL to 1 mg / mL. The composition according to one.
1.5 The composition comprises an additional active ingredient dissolved in the carrier, wherein the additional active ingredient optionally contains antibiotics, anti-inflammatory agents, analgesics, anesthetics, immunosuppressants and antiallergic agents. The composition according to any one of the preceding items, selected from the group consisting of agents.
1.6 The carrier further comprises a co-solvent, the co-solvent being preferably an alcohol or a non-polar solvent, and optionally 38% (w / w) or less relative to the amount of the carrier. The composition according to any one of the preceding items, which is an amount.
1.7 The composition according to any one of the preceding items, wherein the carrier comprises a non-polar solvent or an excipient.
1.8 The amount of the non-protic solvent or excipient is 38% (w / w) or less relative to the amount of the carrier, or 30% (w / w), 25% relative to the total weight of the carrier. (W / w), 15% (w / w) or 10% (w / w), or 5% (w / w) 2% (w / w), or about 1.0% (w / w) or less The composition according to item 1.7, which is the amount of.
1.9 The composition according to claim 1.7 or 1.8, wherein the non-polar co-solvent is selected from any one or a mixture of saturated hydrocarbons; mineral oil; paraffin; siloxane; and perfluorocarbons.
1.10 The composition according to any one of the preceding items, wherein the composition is essentially water-free.
1.11 The composition comprises an iodine seed from the group consisting of any one or a combination of iodine (I-), triiodate (I3-), iodine (IO3-), or hypoiodate (IO-). No, the composition according to any one of the preceding items.
1.12 The composition is non-colorable and optionally the composition is stable at room temperature for at least 30 days, preferably at least 90 days, or more preferably at least 180 days. The composition according to any one of the preceding items, which is stable.
1.13 The composition according to any one of the preceding items, wherein the composition comprises a carrier consisting of an iodine molecule and an alkane hemifluoride.
1.14 The alkane hemifluoride has the formula (II) :.
CF ₃ (CF ₂ ) _n- (CH ₂ ) _m CH ₃ equation (II)
(In the formula, n and m are each independently selected from an integer of 3 to 10), and optionally, the alkane hemifluoride is CF ₃ (CF ₂ ) ₃ . -(CH ₂ ) ₄ CH ₃ (F4H5), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₅ CH ₃ (F4H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₅ CH ₃ (F6H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₇ CH ₃ (F4H8), CF ₃ (CF ₂ ) _7- (CH ₂ ) ₇ CH ₃ (F8H8) and CF ₃ (CF ₂ ) _9- (CH ₂ ) ₄ CH ₃ (F10H5), or more preferably CF ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ ( Selected from F4H5) and CF ₃ (CF ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8),
The composition according to any one of the preceding items.
1.15 The alkane hemifluoride has the formula (II) :.
CF ₃ (CF ₂ ) _n- (CH ₂ ) _m CH ₃ equation (II)
(In the formula, n is an integer selected from 2 to 9 and m is an integer of 1 to 7), which is an alkane hemifluoride, and optionally, the alkane hemifluoride is CF. ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ (F4H5), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₅ CH ₃ (F4H6), CF ₃ (CF ₂ ) ₅ -CH ₂ CH ₃ ( F6H2), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₅ CH ₃ (F6H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8), CF ₃ (CF ₂ ) _3- ( CH ₂ ) ₇ CH ₃ (F4H8), CF ₃ (CF ₂ ) _7- (CH ₂ ) ₇ CH ₃ (F8H8) and CF ₃ (CF ₂ ) _9- (CH ₂ ) ₄ CH ₃ (F10H5) The composition according to any one of the preceding items.
1.16 The composition is dissolved in a carrier consisting of 1-perfluorohexyl-octane or 1-perfluorobutyl-pentane, and optionally a non-polar solvent, up to about 1. The composition according to any one of the preceding items, which comprises a 0 mg / mL iodine molecule.
1.17 One of the preceding items, wherein the composition comprises up to about 0.5 mg / mL iodine molecules dissolved in a carrier consisting of perfluorohexyl-ethane and optionally a non-polar solvent. The composition according to.
1.18 The composition according to any one of the preceding items, wherein the composition is formulated as a liquid, semi-solid, cream, lotion, ointment, or swab.
1.19 The composition according to any one of the preceding items for use as a drug.
1.20 The composition according to item 1.19 for use as a disinfectant and / or disinfectant in the treatment or prevention of a disease or condition in a subject in need thereof.
1.21 The composition is
a) Skin or mucosal tissue; or b) For use in the treatment or prevention of diseases or conditions affecting the eye or eye tissue, wherein the composition is topically administered to the organ or tissue, item 1. The composition according to any one of .19 and 1.20.
1.22 The disease or condition is associated with or caused by a microorganism, the microorganism being preferably selected from any one or combination of bacteria, Demodex, fungi, or viruses. , The composition for use according to any one of items 1.20 or 1.21.
1.23 The composition is
a) Eyelid inflammation, bacterial conjunctivitis, dry eyes, follicular conjunctivitis, giant papillary conjunctivitis, corneal ulcer, keratitis, conjunctivitis neoplasia, HSV keratitis, eye allergy, ulcerative infectious keratitis, epithelial keratitis , Diseases or conditions of the eye or eye tissue selected from the group consisting of interstitial keratitis, neoplastic conjunctivitis and epidemic keratitis;
b) For use in the treatment or prevention of skin, epithelial or mucosal tissue disorders or conditions selected from wounds, cuts, surgical wounds, burns, abrasions, lacerations, ulcers, rashes, erosions, contusions, and infectious diseases. , The composition for use according to any one of items 1.19 to 1.22.
1.24 Item 1. The therapeutic or prophylactic use comprises topically administering the composition to a tissue at any one or more stages before, during, or after surgery or medical procedure. The composition for use according to any one of 19 to 1.23.
1.25 A method of treating or preventing a disease or condition associated with or caused by a microorganism, wherein the microorganism is preferably selected from any one or a combination of bacteria, genus Acne, fungi, or viruses. The method is directed to the composition according to any one of items 1.1 to 1.18, preferably the skin or mucosal tissue (muscosal virus), or eyes or eyes of the subject in need thereof. Containing topical administration to ocular tissue, preferably the composition inhibits or prevents infection or microbial growth, and optionally, the composition comprises a) before, b), or optionally after surgery or medical treatment. c) A method of administration in any one of the subsequent steps or combinations.
1.26 The use of the composition according to any one of items 1.1 to 1.18 in the manufacture of a pharmaceutical for use in the treatment of a disease or condition associated with or caused by a microorganism. The microorganism is preferably selected from any one or combination of bacteria, genus Acne, fungi, or viruses; preferably, the drug is topically administered to the subject and / or the skin tissue, mucosa of the subject. Suitable for topical administration to tissues, eyes or eye tissues, use.
1.27 The use of the composition according to any one of items 1.1 to 1.18 as a disinfectant or disinfectant, preferably the composition is on a biological surface and / or an inanimate surface. Administered, used.
1.28 The use of the composition according to any one of items 1.1 to 1.18 as a disinfectant for an inanimate surface, preferably the inanimate surface is a surgical instrument or means. Is the surface of the use.
1.29 Use of the composition according to any one of items 1.1 to 1.18 in a cosmetological preparation.
1.30 A kit comprising the composition according to any one of items 1.1 to 1.18, wherein the kit is a suitable container for holding and / or storing the composition and a container thereof is required. A kit comprising a dispenser suitable for topical administration of the composition to a subject or surface.

The following examples are intended to illustrate the invention by way of example, but they should not be understood as limiting the scope of the invention.

<Example 1>
Composition (A) I ₂ in F4H5
Iodine molecules in alkane hemifluoride F4H5 at target concentrations of 0.01 mg / ml, 0.05 mg / ml, 0.1 mg / mL, 0.5 mg / mL, 0.55 mg / ml and 0.94 mg / mL (I) ₂ ) A solution was prepared. After weighing the iodine molecule into a clear glass vial, the calculated volume of alkane hemifluoride F4H5 was added. The composition was stirred at room temperature for 2 hours. The composition provides a clear pink solution, ranging from a deep pink / violet color at high concentrations (0.55 mg / ml) to a very light pinkish color at lower concentrations (0.01 mg / ml). is.

A solution of 0.94 mg / mL by adding additional F4H5 to the composition containing 1.0 mg / mL iodine molecules until all residual iodine molecular particles are dissolved to provide a clear solution of dark pink / violet color. Was prepared.

(B) I ₂ in F6H8
Iodine molecule (I ₂ ) solutions in alkane hemifluoride F6H8 were prepared at target concentrations of 0.1 mg / mL, 0.5 mg / mL and 1.0 mg / mL. After weighing the iodine molecule into a clear glass vial, the calculated volume of alkane hemifluoride F6H8 was added. The composition was stirred at room temperature for 2 hours.

The compositions at concentrations of 0.1 mg / mL and 0.5 mg / mL provide a clear pink solution, from dark pink / violet to lower concentrations (0.1 mg) at high concentrations (0.50 mg / ml). / Ml) ranged to a pale pink color.

Additional F6H8 was added to the targeting 1.0 mg / mL composition until all residual iodine molecular particles were dissolved to provide a clear solution at a concentration of approximately 0.88 mg / mL. The solution is a deep pink / violet color.

(C) I ₂ in perfluorodecalin (octadecafluorodecalin, C10F18)
After weighing the iodine molecule into a clear glass vial, a 0.2 mg / mL iodine molecule (I ₂ ) solution in perfluorodecalin was prepared by adding the calculated volume of perfluorodecalin. The composition was stirred overnight at room temperature to give a clear pink solution.

(D) I ₂ in F8H8 or F5H10
After weighing the iodine molecule into a clear glass vial, the calculated amount of alkane hemifluoride is added to the vial to give the composition of 0.2 mg / mL iodine molecule (I ₂ ) and F8H8 as well as 0.1 mg. A composition of / mL iodine molecule (I ₂ ) and F10H5 was prepared, respectively. Iodine molecules were dissolved in each alkane hemifluoride by stirring with heating in a water bath (45 ° C.) to give a clear pink solution. When cooled to room temperature, the composition prepared with F8H8 provided a pinkish semi-solid, while the composition with F10H5 resulted in a pinkish solid. When applied to the skin, both compositions were observed to change to a liquid state upon contact with the skin.

(E) I ₂ in F4H5 + EtOH
A solution with a higher concentration of I ₂ can be prepared by the addition of ethanol (non-anhydrous or alternative anhydrous). A concentration of about 20 mg / mL I ₂ in F4H5 is achieved when ethanol is added to an amount of 38% (w / w) relative to the weight of the F4H5 / EtOH-carrier. The resulting composition is a reddish brown solution.

Add 3 mg / mL iodine by adding 1.5% (w / w) ethanol (or alternative 1.0% (w / w)) to the weight of the F4H5 / EtOH-F4H5 / EtOH liquid carrier. A solution containing was prepared. The composition is a brown-pink transparent solution.

(F) I ₂ in F6H8 + EtOH
A solution with a higher I ₂ concentration can be prepared by the addition of F6H8 / EtOH-ethanol (non-anhydrous or alternative anhydrous). A concentration of about 20 mg / mL I ₂ in F6H8 is achieved when ethanol is added to an amount of 38% (w / w) relative to the weight of the carrier.

Add 3 mg / mL iodine by adding 1.5% (w / w) ethanol (or alternative 1.0% (w / w)) to the weight of the F6H8 / EtOH-F6H8 / EtOH liquid carrier. Prepared to contain. The composition is a reddish brown transparent solution.

<Example 2>
Composition Stability A saturated iodine solution of I _{2 (0.94 mg / mL) in F4H5 and I 2 (} 0.88 mg / mL) in F6H8 prepared in Example 1 above was covered without protection from light. In a transparent glass vial, the mixture was allowed to stand under ambient atmosphere and temperature conditions and stored for 52 weeks. No visible changes were observed in the color or appearance of the particles formed either in the solution or on the glass wall.

In contrast, particle formation in the solution and on the glass wall was observed for the iodine solution of _I2 in the F4H5 / ethanol or F6H8 / ethanol liquid carrier prepared in Example 1 above.

Iodine (I ₂ ) was dissolved in alkane hemifluoride F4H5 and F6H8 at additional concentrations of 0.01 mg / mL, 0.05 mg / mL, 0.1 mg / mL, 0.5 mg / mL and 0.9 mg / mL. The stability of the composition stored in a closed clear glass crimp cap vial (minimum composition volume of 10 mL) is tested. Comparative compositions such as those with alternative carriers such as aqueous and other organic compounds are also formulated and tested for comparison.

Samples of the composition are stored in ambient conditions (room temperature), while some samples are subjected to aging or stress condition testing, eg UV stress conditions (to assess photosensitivity) or non-ambient temperatures.

The composition is evaluated at intervals over time, for example via: precipitation, formation of deposits, etc., as well as for observing and recording any visual changes to the composition, such as color testing. Visual inspection of vials; eg, ultraviolet-visible measurements, and measurement of iodine molecule (and other iodine species) content by other analytical methods in the art for analyzing iodine content.

<Example 3>
Antibacterial effect (A) Ph. Eur. 5.1.3.
Solutions of I _{2 (0.85 mg / mL) in F4H5 and I 2 (} 0.85 mg / mL) in F6H8 to the current version of Ph. Eur. The effectiveness of antibacterial preservation was tested under acceptable criteria for parenteral, ocular, intrauterine and intramammary preparations according to 51.3. Both solutions were found to be in full compliance with the guidelines. The following microorganisms: Pseudomonas erginosa, Staphylococcus aureus, Candida albicans, and Aspergillus brushliensis were used to perform tests on both formulations.

(B) Hemmhof test / agar diffusion test A Hemhof test or an agar diffusion test was performed on the following compositions:
I ₂ (3 mg / mL) solution in F6H8 and EtOH 1.5% (w / w) prepared in Example 1 I ₂ in F6H8 and EtOH 1.5% (w / w) prepared in Example 1. (3 mg / mL)

Organisms tested included Staphylococcus aureus ATCC 6538, Pseudomonas erginosa ATCC 9027, Streptococcus pneumonier ATCC 33400, Proteus Mirabilis ATCC 14153, Candida albicans ATCC 10231, Propionibacterium acnes ATCC 11828. It was.

Both formulations exhibited inhibition zones, demonstrating their effectiveness in inhibiting the growth of the organisms tested.

<Example 4>
Coloring Solutions of I _{2 (0.85 mg / mL) in F4H5 and I 2 (} 0.85 mg / mL) in F6H8 were tested for skin coloring. A drop of each composition was administered to the skin of the subject. Upon initial contact with the skin, the pink color characteristic of the compositions was still observed, but disappeared within seconds. No skin coloring was observed. After that, the color did not transfer to the piece of fabric that came into contact with the skin.

In addition to the lower concentration of I ₂ solution in F4H5 or F6H8, the composition of iodine molecules in F8H8, F10H5 and perfluludecalin also also stains the skin when applied topically to the skin. Not observed.

Further coloring tests are performed on cellulose filter paper (Whatman, stock number 1005-070). In the test, one drop (about 50 μL) of each formulation was added to the filter paper. The coloring behavior of the composition was subsequently recorded.

No coloring of the Whatman filter was observed for solutions of I ₂ in F4H5, F6H8, F8H8, F10H5 and perfluludecalin.

When the same test was performed on the composition of I ₂ prepared in F4H5 / ethanol and F6H8 / ethanol liquid support of Example 1, coloring of Whatman filter paper was observed. Yellow-brown spots at the site of administration remained on the filter paper.

<Example 5>
Further Composition-Stability and Coloring Further compositions of iodine molecules in a carrier consisting of an alkane hemifluoride and optionally a co-solvent as summarized in Table 1 below are included in the methods described in Example 1. Therefore, after preparation, their stability and coloration were tested in the same manner as the protocols described in Examples 2 and 4.

Stability-Vials containing the composition were visually inspected to determine stability. Visual inspection was performed immediately after preparation, 1 day and 1 week later. "Yes" in Table 1 indicates an initial pink discoloration of the composition and a record of no visual changes such as precipitation or deposit formation.

Coloring-coloring was evaluated on cellulose filter paper as detailed in Example 4. “None” in Table 1 indicates that no coloring effect was observed by applying the composition sample to the cellulose filter.

The composition of iodine molecules in the carrier based on 4: 1 ratio F6H8 and paraffin wax was a solid formulation.

A composition containing an alkane hemifluoride, an iodine molecule and the exemplary active ingredient cyclosporine was also prepared. The same tests performed on the compositions in Table 1 were performed. These compositions were also found to be stable and non-colorable.

<Example 6>
EpiOcular Eye Irritation Test The following compositions were evaluated in terms of risk of eye irritation. A model of eye irritation, EpiOcular Eye Irritation Test (OCL-200-EIT; MaTek Corporation) was used. EpiOcular's protocol is the new OECTD Test Guideline No. Approved as 492 (Reconstructed human Cornea-like Epithelium (RhCE) test method for identifying chemicals that do not require classification and identification for eye irritation or severe eye damage) Has been done.

The following compositions were evaluated:
(A) 1.0 mg / mL iodine (1000 ppm) in 1-perfluorobutyl-pentane (F4H5)
(B) 1.0 mg / mL iodine (1000 ppm) in 1-perfluorohexyl-octane (F6H8)
(C) 0.5 mg / mL iodine (500 ppm) in 1-perfluorohexyl-ethane (F6H2)

The viability of the test material-treated tissue higher than 60% compared to the negative control treated tissue is classified as non-irritating, and the viability of the test material-treated tissue lower than 60% is considered to be irritating.

These compositions with relatively high concentrations of iodine were unexpectedly found to be non-irritating. Iodine ophthalmic products in the art based on the povidone iodine complex aqueous formulation typically provide significantly lower concentrations of iodine molecules, such as about 2.5 ppm. All tested compositions of iodine molecules in alkane hemifluoride were classified as non-irritating based on this model, (a) 95.4%, (b) 98.4% and (c), respectively. The result was 107.8% tissue viability.

<Example 7>
Ex Vivo Eye Irritation Test (EVEIT)
M. Frentz et al, Altern. to Lab. Anim. , 2008 (36) p 25-32; and N.M. Carrier 1-perfluorohexyl-octane (Composition A) using an Ex vivo eye irritation test (EVEIT) similar to that described in Schrage et al, Graefes Arch Clin Exp Ophthalmol 2012 (250), 1330-1340. ) And a composition containing an iodine molecule (0.25 mg / ml; 250 ppm) in 1-perfluorohexyl-octane, and hyaluronic acid (HYLO-COMOD®) as a reference and 0 as a control. A comparison of the corneal healing process was performed for 0.01% BAC (benzalkonium chloride).

Method. Rabbit corneas were obtained and placed in an artificial anterior ocular chamber and gently filled with serum-free Minimal Essential Medium (Eagle MEM) containing Eagle's salt and HEPES buffer for nutrition. Medium was constantly replenished with a micropump to mimic the physiological conditions of the eye. The culture chamber was maintained at 32 ° C. at a relative humidity higher than 95% under normal air without CO2 replenishment. Five corneas (n = 5) were used per test substance, while two corneas (n = 2) were tested on positive controls.

After 12 hours of stabilization in the culture chamber, the cornea was assessed microscopically to select a cornea with intact epithelium and no opacity. Four small abrasions (2.3-4.3 mm ² ) were applied to the surface of the selected cornea using a corneal drill. All defects were monitored by sodium fluorescein staining (0.17% aqueous solution) and microscopy.

The test substance was administered 1 hour after the induction of corneal erosion and was applied to the apex of the cornea 6 times daily (30-50 μL every 4 hours). A soft tip cannula was placed at the bottom of the keratoscleral region in the culture chamber with continuous suction to remove any excess liquid. The experiment was completed 3 days after application. Using a phase-contrast microscope integrated camera (KY-F1030U, JVC (Bad Vilbel, DE) attached to Z16 APO Microscope (Wetzlar, DE)), biomicroscopic examination images of the cornea were acquired daily to record the corneal healing process. bottom. All defects were monitored with fluorescein sodium stain (0.17% aqueous solution), where yellow-green fluorescence indicates areas of epithelial defects. The erosion was sized using a microscope software tool (DISKUS). At the end of the third day, the experiment was terminated and all corneas were fixed in 3.7% formaldehyde and stained with hematoxylin-eosin dye for microscopic evaluation. To monitor the metabolic activity of the cornea, glucose and lactate concentrations in the outflow medium from the artificial anterior chamber were quantified by photometric measurements.

result. The composition containing the iodine molecule in F6H8 (Composition B) did not impair the corneal healing process after induction of corneal erosion. On the other hand, similar positive results for corneal healing were observed using composition A (F6H8 alone) or standard reference hyaluronic acid composition (HYLO-COMOD®).

No significant difference was found between Composition A and Composition B (containing 250 ppm iodine molecule) in terms of positive corneal healing effect.

Using both compositions with the reference composition (HYLO COMOD®), mechanically induced epithelial erosions were found to be significantly reduced and essentially eliminated after 2 days of treatment. Furthermore, no corneal toxicity based on metabolic activity exhibited by glucose / lactate measurements was observed for these compositions. In significant contrast, a gradual increase in inducible epithelial damage was observed over the three days of the experiment in controls containing 0.01% preservative BAC.

<Example 7>
Antibacterial effect test (F6H2)
A formulation of iodine molecules dissolved in alkane hemifluoride F6H2 (0.01, 0.05, 0.1, 0.25 and 0.5 mg / ml) was tested for antibacterial activity.

Staphylococcus aureus (107 cells) was plated on the Inactive plate. After a short drying time, 100 μl of a formulation of iodine molecules dissolved in perfluorohexyl-ethane (F6H2) was applied to the microorganisms on the plate. After a specific contact time, residual Staphylococcus aureus cells were harvested by shaking with medium and transferred to an agar plate for plating. After overnight incubation at 37 ° C., the cell number of Staphylococcus aureus was determined.

Within a 30 second contact time of Staphylococcus aureus cells on the plate, the iodine formulation (0.01, 0.05, 0.1, 0.25 and 0.5 mg / ml) in F6H2 tested All were observed to cause complete sterilization of all microorganisms. No viable cell count was observed after the overnight incubation step.

Claims (24)

It consists of a) iodine molecule and b) carrier consisting of alkane hemifluoride.
The alkane hemifluoride has the formula (I) :.
CF ₃ (CF ₂ ) _n −R _m formula (I)
(In the formula, n is an integer selected from 1 to 12, R is a linear or branched chain alkyl or cycloalkyl having m carbon atoms, and m is from 2 to 12. It is an alkane hemifluoride (which is the integer of choice),
The iodine molecule is dissolved in the carrier in an amount of up to 1 mg / mL .
Composition. a) Iodine molecule, as well as
b) Carrier consisting of alkane hemifluoride and non-polar co-solvent
Consists of
The alkane hemifluoride has the formula (I) :.
CF ₃ (CF ₂ ) _n -R _m Equation (I)
(In the formula, n is an integer selected from 1 to 12, R is a linear or branched chain alkyl or cycloalkyl having m carbon atoms, and m is from 2 to 12. It is an alkane hemifluoride (which is the integer of choice),
The iodine molecule dissolves in the carrier in an amount of up to 1 mg / mL and
The non-polar co-solvent is selected from any one or a mixture of saturated hydrocarbons, mineral oils, paraffins, siloxanes, and perfluorocarbons.
Composition. The composition according to claim 2, wherein the non-polar co-solvent is present in an amount of 30% (w / w) or less based on the total weight of the carrier . The composition according to claim 2 or 3, wherein the carrier comprises an alkane hemifluoride or a mixture of alkane hemifluoride in an amount of at least 70% (w / w) with respect to the total weight of the carrier . The composition according to any one of claims 1 to 4, wherein the iodine molecule is dissolved in the carrier in an amount of 0.001 mg / mL to 1 mg / mL. The composition according to any one of claims 1 to 5 , wherein the composition is essentially free of water. The composition is free of iodine seeds from the group consisting of any one or combination of iodide (I ⁻ ), triiodate (I ₃ ⁻ ), iodine (IO _3- ), or ^hypoiodate (IO ⁻ ). , The composition according to any one of claims 1 to 6 . The composition according to any one of claims 1 to 7 , wherein the composition is non-colorable. The alkane hemifluoride has the formula (II) :.
CF ₃ (CF ₂ ) _n- (CH ₂ ) _m CH ₃ equation (II)
(In the equation, n and m are each independently selected from an integer of 3-10), alkane hemifluoride.
The composition according to any one of claims 1 to 8. The alkane hemifluoride is CF ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ (F4H5), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₅ CH ₃ (F4H6), CF ₃ (CF ₂ ). ) _5- (CH ₂ ) ₅ CH ₃ (F6H6), CF ₃ (CF ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8), CF ₃ (CF ₂ ) _3- (CH ₂ ) ₇ CH ₃ (F4H8) ), CF ₃ (CF ₂ ) _7- (CH ₂ ) ₇ CH ₃ (F8H8) and CF ₃ (CF ₂ ) _9- (CH ₂ ) ₄ CH ₃ (F10H5).
The composition according to claim 9. The alkane hemifluoride is selected from CF ₃ (CF ₂ ) _3- (CH ₂ ) ₄ CH ₃ (F4H5) and CF ₃ (CF ₂ ) _5- (CH ₂ ) ₇ CH ₃ (F6H8).
The composition according to claim 10 . The composition is CF with 0.01 mg / mL, 0.05 mg / mL, 0.10 mg / mL, 0.25 mg / mL, 0.5 mg / mL, or 1.00 mg / mL iodine molecules. ₃ (CF ₂ ) ₅ -(CH ₂ ) ₇ CH ₃ The composition according to claim 11, which is dissolved in (F6H8). The composition according to any one of claims 1 to 12 , wherein the composition is blended as a liquid, semi-solid, cream, lotion, ointment, or swab. a) Iodine molecule, as well as
b) A carrier consisting of an alkane hemifluoride and optionally a non-polar cosolvent.
Consists of
The alkane hemifluoride has the formula (I) :.
CF ₃ (CF ₂ ) _n −R _m formula (I)
(In the formula, n is an integer selected from 1 to 12, R is a linear or branched chain alkyl or cycloalkyl having m carbon atoms, and m is from 2 to 12. Alkane hemifluoride (which is the integer of choice),
A composition for use as a drug. The composition for use according to claim 14, wherein the composition comprises a carrier consisting of an iodine molecule and an alkane hemifluoride. The composition for use according to claim 14 or 15, wherein the alkane hemifluoride is that of claim 10 or 11. The composition for use according to claim 14, wherein the composition is the composition according to any one of claims 1 to 14. The composition according to any one of claims 14 to 17 , for use as a disinfectant and / or disinfectant in the treatment or prevention of a disease or condition in a subject in need thereof. The composition
A. Skin or mucosal tissue; or b) for use in the treatment or prevention of a disease or condition affecting the eye or eye tissue, wherein the composition is administered topically to the organ or tissue, claim. The composition according to any one of 14 to 18 . The composition for use according to any one of claims 14-19 , for use in the treatment or prevention of a disease or condition associated with or caused by a microorganism. The composition for use according to claim 20 , wherein the microorganism is selected from any one or a combination of bacteria, Demodex, fungi, or viruses. The composition
a) Eyelid inflammation, bacterial conjunctivitis, dry eyes, follicular conjunctivitis, giant papillary conjunctivitis, corneal ulcer, keratitis, conjunctivitis neoplasia, HSV keratitis, eye allergy, ulcerative infectious keratitis, epithelial keratitis , Diseases or conditions of the eye or eye tissue selected from the group consisting of interstitial keratitis, neoplastic conjunctivitis and epidemic keratitis;
b) For use in the treatment or prevention of skin, epithelial or mucosal tissue disorders or conditions selected from wounds, cuts, surgical wounds, burns, abrasions, lacerations, ulcers, rashes, erosions, contusions, and infectious diseases. , The composition for use according to any one of claims 14 to 21 . 23. 22. The therapeutic or prophylactic use comprises topically administering the composition to a tissue at any one or more stages prior to, during, or after surgery or medical procedure. The composition for use according to any one of the following items. Use of the composition according to any one of claims 1 to 13 in a cosmetological preparation.